Sithole had already made history before taking to the court for the quad singles final, having become the first African wheelchair tennis player to reach a Grand Slam singles final. However, with the world No. 3 having beaten American world No. 1 David Wagner in the round-robin phase of the event on Friday, Wagner's bid to avenge that loss started well as he won four of the last five games in the opening set. But Sithole ended up taking the 3-6, 6-4, 6-4 victory.
Sithole gained the first service break of the second set to lead 4-3, but Wagner matched his opponent and after a sequence of three successive breaks Sithole secured the crucial hold to level the match.
Another service hold at a crucial time came in the eighth game of the deciding set as Sithole opened up a 5-3 lead and Wagner was unable to get back on terms, with Sithole sealing the victory for his fourth win over Wagner this year to complete a memorable Grand Slam debut.
"I was confident coming into the final," said Sithole after ending Wagner's bid for a third successive US Open singles title.
"I'd like to thank the supporters and also David for sharing the experience with me on court. I really enjoy playing against him. He is a great player, one of the best in the quads."